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Omalizumab reverses the phenotypic and functional effects of IgE-enhanced Fc epsilonRI on human skin mast cells. 2007

Gregorio Gomez, and Sherryline Jogie-Brahim, and Mika Shima, and Lawrence B Schwartz
Department of Internal Medicine, Division of Rheumatology, Allergy, and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA.

The dramatic effects of the anti-IgE mAb omalizumab to lower free IgE levels and Fc epsilonRI levels on basophils contrast with more modest clinical effects. Accordingly, whether IgE modulates Fc epsilonRI levels and Fc epsilonRI-dependent mediator release in vitro on human skin mast cells (MC(TC) type) that had matured in vivo is of interest. IgE reversibly enhanced Fc epsilonRI levels on MC(TC) cells in a dose- and time-dependent manner (up-regulation t(1/2) of 4-5 days with 1-3 microg/ml IgE), without affecting cell proliferation. A molar ratio of omalizumab to IgE of 0.9 at baseline prevented receptor up-regulation by 50%, whereas adding omalizumab to MC(TC) cells already with IgE-enhanced Fc epsilonRI levels at molar ratios of 5, 12.5, and 31 reduced Fc epsilonRI levels to baseline with respective t(1/2) values of 8.7, 6.3, and 4.8 days. MC(TC) cells with IgE-enhanced Fc epsilonRI levels were more sensitive to stimulation with a low dose of anti-Fc epsilonRI mAb in terms of degranulation and production of PGD(2), GM-CSF, IL-6, IL-13, and TNF-alpha. Reducing up-regulated Fc epsilonRI levels with omalizumab also reduced mediator release to a low dose of anti-Fc epsilonRI mAb to baseline by 3-4 wk. Thus, reducing free IgE should decrease the hypersensitivity of allergic individuals to low naturally occurring concentrations of allergens.

UI MeSH Term Description Entries
D006967 Hypersensitivity Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. Allergy,Allergic Reaction,Allergic Reactions,Allergies,Hypersensitivities,Reaction, Allergic,Reactions, Allergic
D007073 Immunoglobulin E An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE). IgE
D008407 Mast Cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR. Basophils, Tissue,Basophil, Tissue,Cell, Mast,Cells, Mast,Mast Cell,Tissue Basophil,Tissue Basophils
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000069444 Omalizumab An anti-IgE, recombinant, humanized monoclonal antibody which specifically binds to the C epsilon3 domain of IMMUNOGLOBULIN E, the site of high-affinity IgE receptor binding. It inhibits the binding of IgE to MAST CELLS and BASOPHILS to reduce the severity of the allergic response and is used in the management of persistent allergic ASTHMA. Xolair
D000888 Antibodies, Anti-Idiotypic Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies. Anti-Antibodies,Anti-Idiotype Antibodies,Antibodies, Internal Image,Antigamma Globulin Antibodies,Antiglobulins,Anti Antibodies,Anti-gamma Globulin Antibodies,Anti Idiotype Antibodies,Anti gamma Globulin Antibodies,Anti-Idiotypic Antibodies,Antibodies, Anti,Antibodies, Anti Idiotypic,Antibodies, Anti-Idiotype,Antibodies, Anti-gamma Globulin,Antibodies, Antigamma Globulin,Globulin Antibodies, Anti-gamma,Globulin Antibodies, Antigamma,Image Antibodies, Internal,Internal Image Antibodies

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